Infectious diseases of keratinized tissues are a difficult problem for medical treatment. Keratins are a class of scleroprotein that serve as the major protein components of hair, wool, nails, the organic matrix of the enamel of teeth, horns, hoofs, and the quills of feathers. These proteins generally contain large quantities of the sulfur-containing amino acids, particularly cysteine. Keratins provide a tough, fibrous matrix for the tissues in which they are found. These proteins are characterized as being extremely water insoluble. Because keratins contain few polar amino acids, there is little or no moisture content in the tissues they form. This presents difficulties for the medical treatment of infected keratinized tissues because medicaments are not easily delivered into this type of tissue.
By way of example, onychomycosis is clinically defined as an infection of the nail plate caused by any fungus, including dermatophytes, non-dermatophytes and yeasts. This disease accounts for up to 50% of all nail disease and affects 2% to 18% or more of the world's population. There are four clinical types of onychomycosis: (1) distal subungual onychomycosis, (2) proximal subungual onychomycosis, (3) white superficial onychomycosis, and (4) candidal onychomycosis. The target sites for the treatment of onychomycosis reside in the nail plate, nail bed and nail matrix. Characteristically, infected nails coexist with normal-appearing nails.
The most common form of treatment for onychomycosis is the oral administration of terbinafine (Novartis International AG, Basel, Switzerland) or itraconazole (Janssen Pharmaceutical Products, L.P., Titusville, N.J.). These drugs dominate the current market for the treatment of onychomycosis.
However, there is a need for the development of other forms of treatment. Hay, R J (British Journal of Dermatology 145(S60):3-11, 2001) teaches that these drugs have a clinical failure rate of approximately 25-40%. In addition, both drugs carry label precautions about potential organ toxicity and interactions with common prescription and non-prescription drugs. The Physicians Desk Reference (2003) teaches that rare cases of hepatic failure (including death) have been reported following oral treatment with Terbinafine and Itraconazole. Rare cases of serious cardiovascular events, including death, also have been associated with Itraconazole (Id.). Treatment times are long (several months) and costly. Hay, 2001 teaches that 5-10% of the nail surface still remains abnormal even with a full cure (defined by negative re-culturing). Mandell et al (Principles and Practice of Infectious Diseases, Fifth edition, Chapter 257 by Hay R. J., p. 2765, 2000) teach that the relapse rate is 40%. Treatment options using topical agents are usually of little benefit, and chemical or surgical removal of the infected nail(s) are not adequate therapies, since these treatments can lead to nail bed shrinkage and dorsal dislocation of the nail bed.
Thus, there remains a need in the art to develop improved methods for the treatment of keratinized tissue infected with a pathogen.